rs3737454

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000260.4(MYO7A):c.736-47C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,491,962 control chromosomes in the GnomAD database, including 6,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1554 hom., cov: 33)

Exomes 𝑓: 0.071 ( 5028 hom. )

Consequence

MYO7A
NM_000260.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.29

Variant links:

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-77157232-C-A is Benign according to our data. Variant chr11-77157232-C-A is described in ClinVar as [Benign]. Clinvar id is 255667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77157232-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.736-47C>A		intron_variant	Intron 7 of 48	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.736-47C>A	intron_variant	Intron 7 of 48	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.736-47C>A	intron_variant	Intron 7 of 48	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.703-47C>A	intron_variant	Intron 8 of 49	1		ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17966

AN:

152136

Hom.:

1549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0463

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0533

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.0966

AC:

18633

AN:

192972

Hom.:

1402

AF XY:

0.0916

AC XY:

9462

AN XY:

103246

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.0999

Gnomad EAS exome

AF:

0.264

Gnomad SAS exome

AF:

0.0929

Gnomad FIN exome

AF:

0.0440

Gnomad NFE exome

AF:

0.0511

Gnomad OTH exome

AF:

0.0921

GnomAD4 exome

AF:

0.0710

AC:

95129

AN:

1339708

Hom.:

5028

Cov.:

AF XY:

0.0708

AC XY:

47276

AN XY:

668034

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.0987

Gnomad4 EAS exome

AF:

0.280

Gnomad4 SAS exome

AF:

0.0920

Gnomad4 FIN exome

AF:

0.0451

Gnomad4 NFE exome

AF:

0.0537

Gnomad4 OTH exome

AF:

0.0901

GnomAD4 genome

AF:

0.118

AC:

18001

AN:

152254

Hom.:

1554

Cov.:

AF XY:

0.118

AC XY:

8807

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0463

Gnomad4 NFE

AF:

0.0534

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.0767

Hom.:

385

Bravo

AF:

0.131

Asia WGS

AF:

0.192

AC:

665

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 11

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.46

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over